反应详情

温度

85 °C

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (Intermediate 5-1; 284 mg, 1.05 mmol) and ethyl 2-(5-chloro-2-methyl-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 3-2; 336 mg, 0.93 mmol) and 2M sodium carbonate (0.757 mL, 1.51 mmol), tetrakis(triphenylphosphine)palladium(0) (66.7 mg, 0.06 mmol) and lithium chloride (69.1 mg, 1.63 mmol) in DME (20 mL) and ethanol (5 mL) was degassed and then stirred at 85° C. After 4 hours further tetrakis(triphenylphosphine)palladium(0) (100 mg) and 2M sodium carbonate (0.5 mL) were added and heating was continued for a further 17 hours (overnight). The reaction mixture was allowed to cool, evaporated and partitioned between EtOAc (100 mL), water (50 mL) and 2M HCl (10 mL). The aqueous phase was re-extracted with EtOAc (100 mL), the combined organic extracts were dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-5-methylbiphenyl-4-yl)acetate (288 mg, 70.6%) as a yellow solid.

1. temperatureheating
2. custom(overnight)
3. temperatureto cool
4. customevaporated
5. custompartitioned between EtOAc (100 mL), water (50 mL) and 2M HCl (10 mL)
6. extractionThe aqueous phase was re-extracted with EtOAc (100 mL)
7. dry with materialthe combined organic extracts were dried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto afford crude product
11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane
12. customPure fractions were evaporated to dryness